According to recent studies, nitric oxide (NO), a diatomic free radical produced in vivo, is known to be a material playing very important roles in various physiological processes, such as vasodilation, neurotransmission, blood vessel formation, phagocytosis, wound healing, prevention of thrombus formation, prevention of myocardial damage, and immune response. For example, the anti-thrombotic characteristics of the vascular surface are mainly due to the nitric oxide produced in the endothelial cells of the blood vessel inner wall. Nitric oxide produced in the inner wall inhibits the activation and aggregation of platelets by controlling the flow and pressure of the blood. Furthermore, nitric oxide produced in the phagocytic cells fights against micro-organic materials, such as bacteria penetrated into the body. Since nitric oxide facilitates the dilation and formation of blood vessels in addition to these characteristics, nitric oxide is effective in the treatment of wounds, particularly skin that has been burned, and may also prevent bacteria from entering the wound to reduce the risk of infections.
Due to the discovery of the importance of the physiological role of nitric oxide, studies on a method for not only stably storing nitric oxide in a material, but also exactly transferring nitric oxide to a site to be transferred have also been actively carried out. Various materials capable of storing and transferring nitric oxide have been reported. Nitric oxide may be stored in various materials from small molecules to dendrimers, liposomes, nanoparticles, carbon nanotubes, porous particles, and micelles according to the use.
There are many nitric oxide storing materials like this, but in fact, there are not so many materials which may be directly applied to the living body. Among materials capable of storing and transferring nitric oxide or materials having functionality, a material, which is excellent in biocompatibility and may be utilized in the medical field, is nanofiber. Nanofiber has a structure which is similar to the network structure in vivo in shape, so that studies in that nanofiber exhibits excellent effects at the time of cell culture have been performed, and even in fact, nanofiber tends to be used most frequently in the medical field. Nanofiber is so low in production rate that nanofiber has not been widely nor industrially used until recently, but nanofiber did not come into the spotlight until the mid-1990s when an electrospinning device used in the production of nanofibers was simplified.
Since the electrospinning process employs simpler devices than other production technologies and spinning may be achieved even when most of the polymer solutions or melts are used in a small amount, studies for imparting various structures and functionalities have been actively conducted. If nitric oxide, which is in charge of inducing essential roles in vivo and has been verified of being capable of artificially performing these roles, is added to nanofiber having many advantages as described, advantages presented by both the nanofiber and nitric oxide may be maximally utilized. Studies on nanofibers capable of storing and transferring nitric oxide are still in the initial step and many research results have not been published, so that the studies are expected to be actively conducted in the future.
When several research results are simply introduced, first, there is a method of mixing small molecules capable of storing nitric oxide with a polymer capable of being electrospun by a physical method, and then producing nanofibers (Coneski, P. N.; Nash, J. A.; Schoenfisch, M. H. ACS Appl. Mater. Interfaces. 2011, 3, 426-432). When nanofibers are produced by this method, molecules which store nitric oxide physically included in the nanofibers are likely to easily escape out of the nanofibers. Even though nanofibers are produced by using polymer materials known to be biocompatible, there is a problem in that it is impossible to know what side effects a nitric oxide storing material, which has escaped therefrom, may cause.
Next, there is a method of producing nanofibers by using a material in which nitric oxide is stored in the form of S-nitrosothiol (RSNO) (Wold, K. A.; Damodaran, V. B.; Suazo, L. A.; Bowen, R. A. ACS Appl. Mater. Interfaces. 2012, 4, 3022-3030). The method is a method of storing nitric oxide by using a chemical reaction to convert a functional group of a polymer into another material and producing nitric oxide in the form of SNO, and refers to RSNO. The method is advantageous in that there are various materials, which may be produced, because the method may be applied to a molecule which is capable of being substituted with the polymer while carrying sulfur at the end of the molecule. However, since S and N of RSNO consist of a very weak sigma bond, there is a disadvantage in that S and N have characteristics of being easily decomposed even by light, so that it is not easy to control release characteristics of nitric oxide.
In order to solve these problems, in the present study, aminoalkoxysilane, which is a material of storing nitric oxide in the form of N-diazeniumdiolate, was used and a polymer having a functional group capable of carrying out a sol-gel reaction with aminoalkoxysilane while being capable of producing nanofiber, was synthesized. Diazeniumdiolate substituted with an amine group is usually present in a stable state while forming a resonance structure, and when a sol-gel reaction of aminoalkoxysilane including the diazeniumdiolate with a polymer capable of being electrospun is carried out, the two materials form a chemical bond by forming a siloxane bridge (Si—O—Si). For this reason, it is possible to prevent aminoalkoxysilane, which stores nitric oxide, from escaping out of the nanofiber, and as a result, the nanofiber may be classified into a nanofiber having excellent biocompatibility.